Elderly patients are increasingly undergoing cardiac surgery and this trend is forecasted to continue. A very common and disturbing consequence of this surgery is deterioration in cognitive function. This impairment can be as high as 83% in the hospital and continue in up to 30% or more of patients for over a year. Elderly patients are particularly susceptible to this neurocognitive consequence of life- preserving surgery. This cause of cognitive dysfunction is postulate to be a result of cerebral emboli that occur during cardiac surgery. The cause of cognitive dysfunction is postulated to be a result of cerebral emboli that occur during cardiac surgery, which are impossible to prevent, and therefore strategies to protect the brain must be developed. It has become standard practice in cardiac surgery to allow the hematocrit advantages to blood flow during hypothermic cardiopulmonary bypass and fear of adverse consequences of transfusion. It is not known whether this hemodilution (50% reduction in oxygen carrying capacity of the blood) contributes to brain injury and cognitive impairment. We will test the hypothesis that preserving oxygen carrying capacity of the blood by limiting the amount of hemodilution during cardiopulmonary bypass improves cerebral protection. A prospective, randomized trial in 370 patients will be conducted in which half of the patients will be assigned to moderate hemodilution (hematocrit of greater than or equal to 27%-treatment group) and other half to profound hemodilution (hematocrit 15-18%-current practice group). Change in cognitive function over the first year after surgery will be compared between the groups. A secondary aim is to determine if serum markers of glial (S100beta) and neuronal (neuron-specific enolase) brain injury predict the changes in cognitive function. A positive association of brain injury markers with cognitive change will allow earlier detection and support the hypothesis that the cognitive changes are a result of brain ischemia. New knowledge gained in this study would be immediately transferred to clinical practice and could reduce the severity of cognitive impairment. The new information regarding cerebral protection would also have application in all ischemic brain syndromes including stroke.